title: Synthesis and biological evaluation of novel 5-benzylidenethiazolidine-2,4-dione derivatives for the treatment of inflammatory diseases.
abstract: Twenty-two compounds based on thiazolidine-2,4-dione moiety were synthesized and evaluated for the inhibitory potency on the production of nitric oxide (NO), inducible nitric oxide synthase (iNOS) activity, and the generation of prostaglandin E(2) (PEG(2)). (Z)-N-(3-chlorophenyl)-2-(4-((2,4-dioxothiazolidin-5-ylidene) methyl) phenoxy) acetamide (3I), superior to the commercial anti-inflammatory drug indomethacin, significantly inhibited iNOS activity (IC(50) = 8.66 μM), iNOS-mediated NO, and cyclooxygenase (COX)-2-derived PGE(2) production (IC(50) = 4.16 and 23.55 μM, respectively) on lipopolysaccharide (LPS)-induced RAW 264.7 cells. Docking study revealed that 3I was perfectly docking into the active site of murine iNOS and suppressed the expression of iNOS protein as evidenced by Western blot analysis. At the dose of 50 mg/kg, oral administration of 3I possessed protective properties in both carrageenan-induced paw edema and adjuvant-induced arthritis rat models.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Gaopeng Street, Chengdu 610041, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.forename: Caifeng
authors.initials: C
authors.lastname: Xie
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Ma
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Mingli
authors.initials: M
authors.lastname: Xiang
authors.forename: Xia
authors.initials: X
authors.lastname: Ye
authors.forename: Hao
authors.initials: H
authors.lastname: Zheng
authors.forename: Zhizhi
authors.initials: Z
authors.lastname: Chen
authors.forename: Qinyuan
authors.initials: Q
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Jinying
authors.initials: J
authors.lastname: Chen
authors.forename: Jincheng
authors.initials: J
authors.lastname: Yang
authors.forename: Neng
authors.initials: N
authors.lastname: Qiu
authors.forename: Guangcheng
authors.initials: G
authors.lastname: Wang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liang
authors.forename: Aihua
authors.initials: A
authors.lastname: Peng
authors.forename: Shengyong
authors.initials: S
authors.lastname: Yang
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D001169:Arthritis, Experimental / Q000188:drug therapy; D001597:Benzylidene Compounds / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D002351:Carrageenan / Q000494:pharmacology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008958:Models, Molecular; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D051381:Rats; D045162:Thiazolidinediones / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D000893:Anti-Inflammatory Agents; D001597:Benzylidene Compounds; D008070:Lipopolysaccharides; D045162:Thiazolidinediones; D009569:Nitric Oxide; D002351:Carrageenan; C089946:2,4-thiazolidinedione; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone